Role of TfR2-Y250X and TfR1- rs3817672 Single Nucleotide Polymorphism on Pathophysiology of Iron Deficiency Anemia

Abstract

Background: Transferrin receptor (TfR) is a carrier protein for transferrin. It is regulated in response to intracellular iron concentration and plays a role for the import of iron into the cell. The transferring receptor 2 (TFR2) gene showed homology to transferrin receptor 1 (TFR1) gene and encodes a transmembrane protein with a large extracellular domain, which is able to bind transferrin. Mutations in transferrin receptors (TfR2 and TfR1) may alter the pathophysiology of iron deficiency anemia. Alteration in genes encoding transferring receptor cause change in iron homeostatsis and provides a tool for investigating the excess iron absorption and abnormal iron distribution in iron related disorders. However the clinical significance of the interaction of transferring mutations with iron deficiency anemia remains unclear. Thus, the objective of my study was to investigate the effect of TFR1 and TFR2 genotypes on pathophysiology of iron deficiency anemia.

Study design: Study subjects were 460 iron deficiency anemia patients and 500 age and sex-matched healthy controls. Transferrin receptor, ferritin and CRP analysis was done by ELISA method while ESR analysis was done according to Wintrobes's method. CBC analysis was done by auto-analyzer. TFR1-rs3817672 SNP and TFR2 (Y250X) mutation was analyzed by using PCR RFLP method.

Results: Amongst the iron deficiency anemia patients, 13 were heterozygous and five were homozygous for rs3817672 SNP. TFR2 (Y250X) mutation was detected in 6 patients with heterozygous conditions. None of the patients were presenting homozygous condition while four controls were presenting heterozygous and one with homozygous condition. Controls were presenting 3% and 0.6% of TFR1 rs3817672 SNP heterozygosity respectively.

Conclusion: TfR2 -Y250X and TfR1-rs3817672 SNP showed clinical association with iron deficiency anemia and screening for mutations of TFR2 is a new diagnostic tool that can be offered to patients who do not have HFE mutations or who have incomplete HFE genotypes. This results may have practical implications for the molecular diagnosis of hemochromatosis. Genotyping the TFR gene should be included in the disease diagnostic protocols.